Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study

J Alzheimers Dis. 2016;51(2):451-61. doi: 10.3233/JAD-150991.


Background: Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts.

Objective: We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer's disease (AD), MRI markers of brain aging, and neuropsychological function.

Methods: Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort-specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139).

Results: In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (β= -0.03 to -0.05±0.02) and the Hooper Visual Organization Test (β= -0.09 to -0.12±0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (β= -0.01±0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD.

Conclusions: In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function.

Keywords: Alzheimer’s disease; brain; dementia; diet; lifestyle; magnetic resonance imaging; neuropsychology; nutritional status; risk factors; vitamin D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / blood
  • Aging / pathology
  • Brain / diagnostic imaging*
  • Cohort Studies
  • Dementia / blood*
  • Dementia / diagnostic imaging
  • Dementia / epidemiology*
  • Female
  • Humans
  • Incidence
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuropsychological Tests
  • Regression Analysis
  • Risk
  • Sensitivity and Specificity
  • Vitamin D / blood*


  • Vitamin D